Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments.

PURPOSE: To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments. METHODS: A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment. For the first approach, precipitation, as evidenced by the development of turbidity, was induced using the solvent shift method, by mixing concentrated API solutions in DMSO with an aqueous buffer in a capillary. Subsequently, crystallization was monitored in situ over time using synchrotron radiation (simultaneous SAXS/WAXS beamline 12-ID-B at the Advanced Photon Source, Argonne National Laboratories, Argonne, IL). In the second approach, amorphous films were prepared by melt quenching; after adding buffer, crystallization was monitored with time using polarized light microscopy. RESULTS: In general, the crystallization behavior of a given compound was similar irrespective of the experimental method employed. However, the crystallization behavior among different compounds varied significantly, ranging from immediate and complete crystallization to no observable crystallization over biorelevant time scales. Comparison of the observed behavior with previous studies of crystallization tendency in non-aqueous environments revealed that the crystallization tendency of individual APIs was somewhat similar regardless of the crystallization environment. CONCLUSIONS: API properties, rather than the method by which amorphous materials are generated, tend to dictate crystallization behavior in aqueous media.

Estudio comparativo de estabilidad de tres formulaciones magistrales de Sildenafil bajo la forma de solución, obtenidas a partir de diferentes productos comerciales / Comparative study stability of the three master formulation of Sildenafil solution obtained from differents trademarks

El Sildenafil es un fármaco de comprobada actividad terapéutica en la disfunción eréctil; se encuentra disponible bajo la forma farmacéutica de tabletas de administración oral. En la actualidad se está formulando magistralmente en forma de so lución oral a una concentración de 1mg/ml, para la hipertensión pulmonar (HP), por lo que se ha planteado realizar un estudio de la estabilidad en tres condiciones: ambientales (25±-2 ºC), de refrigeración (5±3 ºC) y exageradas de almacenamiento (40 ºC ± 2 ºC). Los parámetros evaluados fueron apariencia, limpidez, densidad, pH y contenido de sildenafil. El método analítico empleado fue cromatografía líquida de alta resolución (HPLC) de fase reversa. La apariencia, los valores de pH y densidad de las soluciones obtenidas se mostraron sin cambios significativos, en las diferentes muestras y condiciones de estudio. En cuanto a los resultados del contenido inicial de sildenafil se obtuvo aproximadamente el 75% en peso al formular la solución, partiendo del comprimido. Cabe señalar que se observó discrepancia en los valores de concentración del sildenafil obtenidos en los diferentes tiempos y condiciones; resultados éstos de esperarse por tratarse de una formulación magistral que parte de comprimidos de diferentes casas comerciales, por lo que este estudio permitió sugerir que la formulación magistral se reformule a la forma farmacéutica de suspensión, para garantizar el contenido de todo el principio activo en la misma.

Sildenafil is a drug with proven therapeutic activity in erectile dysfunction is available under the pharmaceutical form of tablets for oral administration. It is currently being de veloped skillfully in an oral solution at a concentration of 1mg/ml, for pulmonary hypertension (pH), as has been planned to perform a study of stability in three conditions: environmental (25 ± 2 ºC), refrigeration (5 ± 3 ºC) and exaggerated storage (40 °C ± 2 ºC). The parameters evaluated were appearance, clarity, density, pH and content of sildenafil. The analytical method used was high performance liquid chromatography (HPLC) reverse phase. The appearance, pH and density of the solutions were no significant changes in the different samples and study conditions. As for the results of the initial content of sildenafil was obtained about 75% by weight in for mulating the solution, based on the tablet. It should be noted that there was discrepancy in the values of concentration of sildenafil obtained at different times and conditions, results they expected because it is a masterly formulation of tablets of different business houses, so this study suggest that the wording allowed masterful be reformulated to the pharmaceutical form of suspension, to ensure the contents of the entire active.

[The modern approaches to the choice of infusion agents used in the treatment of severe injuries and burns].

The article presents an analytical review of modern possibilities of the complex pathogenic treatment for severe traumas and injuries at the expense of systemic use of infusion drugs with antihypoxic and antioxidant effects. It is shown that hypoxia and oxidative stress is the typical; pathologic process that accompanies the development of traumatic disease during severe surgical pathology. One of the effective ways to correct the developing disorders is to use the regulatory or substrate antihypoxants as well as the drugs with antioxidant effect.

Preparing botanical medicines.

Next to dose concerns, the subject of preparation may be the most misinterpreted area of modem botanical medicine. Yet it is one of the most important issues in clinical practice. In traditional medicine systems, any given herb would have been discovered to be effective in specific preparations. The "ideal" form and preparation varies from herb to herb, as well as from person to person. The most desirable preparation is usually defined as the way to get the most active ingredient out of the herb. However, in some cases, the proper preparation may be the only way to safely use the herb. The proper preparation may be dictated by the solubility of the constituents and may also be defined according to how the patient is practicably able to consume it. In today's market, most herbs can be found in most preparations, but that does not mean that every preparation will contain active constituents. The author makes the case that using traditional preparations from the ethnic system of the herb origin will be the most effective clinical course of action.

Light scattering investigations on freeze-dried glucocorticoids in aqueous solution.

Aqueous solutions of three glucocorticoid drug substances were investigated using dynamic light scattering. Evidence of micelle formation was found. The identified diffusion coefficients, micellar radii and the dependence of these parameters on the concentration of the solution as well as on the molecular structure of the drugs are discussed. It is postulated that the micellar character of the solutions is one reason for the ease of lyophilization of such molecules without additional substances.